The two recent prospective randomized trials CARMENA and SURTIME have changed the therapy paradigm of metastatic renal cell carcinoma. The CARMENA trial was conducted to investigate whether cytoreductive nephrectomy (CN) is required in the targeted therapy area, whereas SURTIME studied whether deferred CN in combination with sunitinib can be used to identify patients with inherent targeted therapy resistance. In the current review, we provide a comprehensive discussion of two randomized studies and the current evidence with up-do-date algorithms for treating primary metastatic clear-cell renal cell carcinoma in the era of targeted therapy and immune-checkpoint inhibition.

Background: Cancer types eligible for treatment with immune checkpoint inhibitors (ICI) have increased over the past decade thus simultaneously growing the number of patients presenting to emergency departments (ED) with immune mediated toxicities. Objectives: The objective of this study was to ascertain information regarding the knowledge and management of immune checkpoint inhibitor mediated toxicities amongst emergency department physicians. Methods: A multiple-choice questionnaire was developed assessing the understanding of ICI usage and management of immune mediated toxicities, amongst ED physicians in 6 major ED departments in London. Participating clinicians included all levels of trainees and ED physicians. Questionnaires were distributed during weekly ED educational sessions, followed by training on immune-mediated toxicities. Results: Between March 2019 and September 2019, the questionnaire was delivered to 126 participants (80% junior grade, 20% specialist ED consultants). There was no significant association between clinician's seniority and overall score reached on the questionnaire. Amongst all participants, 56, 49, and 36% identified correctly ICIs as the first-line treatment regimen for melanoma, renal cell carcinoma, and non-small cell lung cancer, respectively. Overall, 90% of the participants recognized correctly cisplatin as a chemotherapy agent and 77% pembrolizumab as an ICI agent. Generally, there was a good understanding of chemotherapy related toxicities, however, the participants scored less well on questions relating to ICIs. Ten months following the initial audit and educational intervention, a single site re-audit was performed. The total average correct score was similar pre- and post-intervention (8, 13%, respectively). Conclusions: Knowledge and management of immune mediated toxicities is inferior compared to chemotherapy across physicians working in major ED departments in London. This survey highlights the need for increased education on ICI amongst ED clinicians.